SCRAPIE USA

Transmissible Spongiform Encephalopathy TSE Prion PrP sheep and goats

My Photo
Name:
Location: BACLIFF, Texas, United States

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Sunday, November 05, 2023

Comparing the Distribution of Ovine Classical Scrapie and Sporadic Creutzfeldt-Jakob Disease in Italy: Spatial and Temporal Associations (2002-2014)

Comparing the Distribution of Ovine Classical Scrapie and Sporadic Creutzfeldt-Jakob Disease in Italy: Spatial and Temporal Associations (2002-2014) 


Ru G1 ., Pocchiari M2 ., Bertolini S. 1, Pite L.1 , Puopolo M.2 , Ladogana A.2 , Perrotta M.G.3 , Meloni D 1 . (1) National reference center for the study and research on animal encephalopathies and comparative neuropathologies (CEA). Experimental Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, Torino, Italy. 

(2) Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy. (3) Office 3 National center for the fight and emergency against animal diseases. Ministry of Health, Roma, Italy. 

Aim: This study aims to investigate potential spatial and temporal associations between Creutzfeldt-Jakob disease (CJD) in humans (2010-2014) and ovine classical scrapie (CS) (2002- 2006) in Italy, serving as a proxy for exposure. 

Materials and Methods: National data from prion disease surveillance in humans (sporadic CJD) and small ruminants (CS) in Italy were utilized. A descriptive geographic analysis was conducted for each disease individually. Subsequently, an ecological study was performed to compare the occurrence of both diseases at the district and regional levels. Standardized incidence ratios (SIR), adjusted for confounders, were calculated for CJD and CS by district and region, respectively, representing the outcome and proxy of exposure. Considering a possible long incubation period of CJD, two study periods were analysed: 2010-2014 for CJD and 2002-2006 for CS. Eight alternative linear regression models were developed using SIR in humans as the dependent variable and SIR in sheep as the independent variable. These models varied in the scale of SIR data (continuous vs. categorical), geographical level (district vs. region), and the potential past exposure of sheep in specific areas to a known source of infection (via a contaminated vaccine). 

Results: The analysis of data at the district level revealed no significant association. However, when considering aggregated regional data, all four models consistently indicated a statistically significant positive association, suggesting a higher incidence of the disease in humans as the regional incidence of sheep scrapie increased. 

Conclusions: While the results are intriguing, it is important to acknowledge the inherent limitations of ecological studies. Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively. 

Funded by: Italian Ministry of Health Grant number: Realizzazione del programma epidemiologico finalizzato a dare evidenza del potenziale zoonotico delle TSE animali diverse dalla BSE. Prot. N. 0018730-17/07/2015-DGSAFCOD_UO-P 

''Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively.''


=====

Transmission of Idiopathic human prion disease CJD MM1 to small ruminant mouse models (Tg338 and Tg501). 

 Enric Vidal1,2, Samanta Giler1,2, Montse Ordóñez1,2, Hasier Eraña3,4, Jorge M. Charco3,4, Guillermo Cantero1,2, Juan C. Espinosa5 , Juan M. Torres5 , Vincent Béringue6 , Martí Pumarola7 and Joaquín Castilla3,8,9 1 Unitat mixta d’Investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia. 2 IRTA. Programa de Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia. 3 Center for Cooperative Research in Biosciences (CIC BioGUNE), Basque Research and Technology Alliance (BRTA), Prion Research Lab, Derio, Spain. 4 ATLAS Molecular Pharma S. L. Derio (Bizkaia), Spain. 5 Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid 28130, Spain. 6 Molecular Virology and Immunology, Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, Jouy-en-Josas, France 7 Unitat de Patologia Murina i Comparada, Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Campus de UAB, 08193 Bellaterra, Barcelona, Catalonia. 8 IKERBASQUE, Basque Foundation for Science, Bilbao 48013, Bizkaia, Spain. 9 Centro de Investigación Biomédica en Red de Enfermedades infecciosas (CIBERINFEC), Carlos III National Health Institute, Madrid, Spain. Corresponding author: enric.vidal@irta.cat Phone: 934674040 (1784) 

Aims: About 90% of Creutzfeldt-Jakob disease cases are classified as sporadic (sCJD), that is, occur infrequently, randomly and without a known cause. It is a fatal neurodegenerative disease with an incidence of 1-1.5 cases per million per year. Epidemiological studies have been so far unable to establish a causal relationship between sCJD and prion diseases in animals. 

The zoonotic potential of sheep scrapie was demonstrated in 2014 (Cassard et al., Nature Communications) through inoculation of transgenic mice overexpressing the human prion protein with scrapie isolates. The resulting prion disease was indistinguishable from that occurring after sCJD inoculation in the same model and, while these results do not demonstrate that sCJD is caused by scrapie prions, they do show that the transmission barrier between ovine and human prions is not absolute. Our aim is to further assess this zoonotic risk. 

Materials and methods: we have prepared inocula from 3 sCJD cases (MM1, MV2 and VV2) and 2 VPSPr cases (MM and MV) to verify if it is possible to recover the scrapie phenotype upon inoculation in Tg338 and Tg501 ovinized mouse models. Additionally, two different inocula gCJD (E200K) and GSS (A117V) have been also included in the bioassays as controls for classical and atypical genetic human prions, respectively.

Results: No evidence of transmission was found on a first passage in Tg338 nor Tg501 ovinized mice, but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12 Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed. 

Funded by: MINECO grant number AGL2017-88535-P and PID2021-1222010B-C22 and by Interreg POCTEFA grant number EFA148/16 (RedPRION)

''but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12 Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed.''


Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.


***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.


***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.



O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 

PRION 2015 CONFERENCE


***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 1933-690X 

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 


FRIDAY, JANUARY 20, 2023 

EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES 


WEDNESDAY, FEBRUARY 03, 2021 

Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al


WEDNESDAY, MARCH 16, 2022 

SHEEP BY-PRODUCTS AND WHAT ABOUT Scrapie TSE PrP and Potential Zoonosis? 


WEDNESDAY, DECEMBER 8, 2021 

Importation of Sheep, Goats, and Certain Other Ruminants AGENCY: Animal APHIA, USDA, FINAL RULE [Docket No. APHIS–2009–0095] RIN 0579–AD10


FRIDAY, DECEMBER 10, 2021 

USDA APHIS National Scrapie Eradication Program October 2021 Monthly Report Fiscal Year 2022


MONDAY, NOVEMBER 29, 2021 

Experimental Oronasal Transmission of Chronic Wasting Disease Agent from White-Tailed Deer to Suffolk Sheep Volume 27, Number 12—December 2021 Dispatch


FRIDAY, DECEMBER 10, 2021 

Scrapie at Abattoir: Monitoring, Control, and Differential Diagnosis of Wasting Conditions during Meat Inspection 


BSE: TIME TO TAKE HB PARRY SERIOUSLY

HB Parry Seriously’ (YB88/6.8/4.1) IF the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. https://web.archive.org/web/20030714133556/http://www.bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf


1988: Letter entitled ‘Scrapie, Time to take HB Parry Seriously’ (YB88/6.8/4.1) 24. In this letter I stated that BSE had been officially confirmed as a TSE (when much of the veterinary profession still favoured a variety of alternate hypotheses). I also suggested that scrapie should be made a notifiable disease, and drew attention to the work of HB 'James' Parry and the possibility that natural scrapie in sheep might be of genetic origin. 25. I withdrew the letter following advice from Professor Barlow (who as far as I can recall had been contacted by MAFF and the Veterinary Record) that it might not be in my interests to pursue publication at that moment in time. 26. I received a letter from the then editor, Edward Boden, questioning my permission to release the information that BSE was indeed a proven TSE. I had no permission, though was unaware that any was needed, to inform my profession of this urgent and important fact.

1992: McGill and Wood 27. This paper summarises views as to why an open debate on TSEs and in particular scrapie were and remain essential. We drew attention to the work of Parry, Prusiner and others, and outlined novel explanations for recent research findings in light of such work. We suggested that not all the relevant questions were being asked in the interpretation of data. In particular, the possibility that the infectious agent was being generated de novo from the genome (the PrP gene) in certain families of sheep, was still not being considered, despite a body of scientific data going back over 30 years. It was to be a further 5 years before publications from Government laboratories would start to cite Parry’s work as a possibly correct theory. 28. The refereeing process for this work was at the time not transparent, and I have yet to be informed as to why this remains unpublished.

SNIP...SEE;


1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404


Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6


Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).


Confidential The Scrapie Files and CJD Group 1978





78/6.27/4.1 *** bse inquiry yb cjd and scrapie

1978 Cjd working group begins


78/10.06/2.1 yb 

1979 CJD working group ???

1980 cjd working group ???


CJD and Scrapie 


See more 



Scrapie Field Trial was developed at Mission, Texas, on 450 acres of pastureland, part of the former Moore Air Force Base 

EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES

Academic Preg

James Hourriganl, Albert Klingsporn2, Edited by » Peast

W. W. Clark3, and M, de Camp4

United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services

snip...

METHODS

A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission,

Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods

to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.

The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas:

snip... 

RESULTS

Table 1 indicated that previously exposed sheep brought to the Station at various times and ages (1 to 89 months old) included 333 Suffolks at risk. Of these, 98 (29%) developed scrapie. This demonstrated the necessity to slaughter such sheep to prevent further Spread of the disease, These pre- viously exposed Suffolks were bred at the Station and produced 446 progeny at risk. Of these 153 (34%) developed scrapie.

Although the minimum and average ages when scnapied were similar for both groups, some of the previously exposed Suffolks brought to the Station developed scrapie when much older--ewes 60 to 142 months old and rams 67 to 102 months old. O£ the 153 Suffolks born at the Station, only 3 were more than 60 months of age (65, 66, and 69 months old).

This difference in age scrapied was attributed to the fact that the Suffolks born at the Station may have been sub- ject to a greater exposure from birth.

It was also observed that when both dam and progeny were scrapied, the progeny nearly always developed clinical disease at a younger age than their respective dam. Thirty- two dams were scrapied at an average of 60 months of age. Forty-six of their progeny developed the disease at an average of 38 months (range 25 to 53 months). Thirty-seven of the 46 progeny were younger than the dam (average 20 months younger, range 2 to 99 months younger). Two were scrapied at the same age as their dams, and 8 were older (average 5 months, range 1 to 13 months older).

++. Although the incidence of scrapie was considerably Greater in the progeny of scrapied compared to free dams, the progeny of either scrapied or free dams manifested scrapie at the typical age and irrespective of the age their respective dams were scrapied. The differences in ages that dams and progeny were scrapied was believed due to difference of exposure, particularly whether they were exposed at an early age,

Table 2 summarized the data on exposed Suffolks and was Prepared so as to show scrapie incidence in the progeny of dams and sires of known Scrapie status. The scrapie incidence in the progeny of Free X Free parents was 25%, progeny of scrapied Sires 39%, and scrapied dams 42%. When both sire and dam were scrapied, the scrapie incidence in 18 Progeny at risk was 78%.

When the scrapie status of the sire was ignored, scrapie incidence in th- progeny of free dams was 34% and in pre y of scrapied da as 62%. When the scrapie status of the dam was ignored, scrapie incidence in the progeny of free sires was 26% and in the progeny of scrapied sires was 452.

Although the scrapie incidence was nearly double in the progeny of scrapied compared to free dams, the latter con- tributed a greater number of scrapied progeny, 116, compared to only 51 cases which had scrapied dams. This was because free dams made a considerably heavier contribution to the progeny at risk4-342 compared to 82. It was felt that in farm flocks a similar situation could exist.

It was possible that free dams could have been mis- classified; however, this was unlikely to have been significant, unless "nonclinical or carrier" dams exist. In this Suffolk group, the ages of 100 free dams of scrapied progeny ranged from 25 to 160 (average 97) months. These free dams did not show clinical signs of scrapie,”and there were no histopathological lesions suggesting scrapie in those which died, If one cannot classify as free, ewes which have reached 97 months (average) and did not develop the disease, from a practical standpoint, it is not possible to classify sheep as free, at least on the basis of clinical signs and histology. The free dams of 50% of the scrapied progeny were more than 100 months of age, averaging 126 months.

Upon arrival at the Mission Station at 3 to 9 months of age, the 140 previously unexposed sheep and goats were placed in infected pastures and corrals and were subjected to con- tact with a succession of natural cases of scrapie in sheep, and eventually also in goats. These animals were bred only within their respective groups and were not crossbred to other breeds of sheep or those brought to the Station from infected flocks or their progeny. The male or female animals mixed freely with animals of their respective sex of the infected Flock and were similarly identified and subjected to similar flock management and diagnostic procedures.

Table 3 indicated that natural scrapie had occurred in 5 of the 140 previously unexposed sheep. One case each occurred in Rambouillet, Targhee, and Hampshire ewes at 88, 89, and 89 months of age and in % Suffolk ewes at 73 and 102 months of age, and 85, 82, 80, 64, and 93 months following initial natural exposure. This represented a natural situation involving lateral spread, under the circumstances involved, when sheep were not exposed when very young. Scrapie was not detected clinicaliy or histologically in any of the dairy or Angora goats brought to the Station. The disease occurred in an average of 27% of the progeny of previously unexposed sheep or goats born at the Station and included cases in progeny of all breeds of sheep or goats taken there, The incidence in the progeny ranged from 14% in Rambouillet sheep to 61% in dairy goats. ~

These data showed that scrapie spread laterally, by contact exposure, from scrapied te previously free animals, but at an apparently lower rate when exposure was first received at the age of 3 to 9 months. These animals were presumed to be susceptible to the disease, as their progeny developed scrapie at rates and ages similar (on the average) to the progeny, pf previously exposed Suffolk sheep born and reared in the same environment.

It was suggested that the progeny of previously unexposed animals developed scrapie at a much higher rate than their parents, and at a younger age, because they were subjected to exposure from birth. The data did not rule out the possibility that the animals born at the Station could have also received the virus from their dams "vertically" prior te, at, or following birth.

Table 4 summarized the scrapie incidence in #he progeny, born at the Station, of previously unexposed dairy goats.

The data were prepared so as to show scrapie incidence in the progeny of dams and sires of known scrapie status.

The 58% incidence in the progeny (24 at risk) of Free X Free parents was more than twice the 25% seen in the Suffolk group (Table 2). Scrapied sires did not increase the incidence in goat progeny (it was 44%); scrapied dams increased the incidence to 71%. When both sire and dam were scrapied the incidence was 89%, with only 9 goat progeny at risk.

When the scrapie status of the sire was ignored, the scrapie incidence in the progeny of free dams was 56% and in the progeny of scrapied dams it was 74%.

Free dams contributed 34 progeny at risk and scrapied dams 31 progeny.

When the scrapie status of the dam was ignored, scrapie incidence was 64% in the progeny of free sires and a similar 66% in the progeny of scrapied sires.

A total of 244 sheep (127 Suffolk, 59 Rambouillet, and 58 Targhee) were removed from scrapie exposure within a few hours of birth or at 4, 9, or 20 months of age and placed in isolation pens. Removal of sheep from exposure at these ages was selected as being representative of usual flock operations when sheep might be sold from an infected flock at weaning, the first fall or the second fall after their birth.

Table 5 reflected the fate of such animals. Four of the 6 scrapied sheep which had been isolated at birth were Suffolks and the 2 older animals were Targhees. The first case in the group isolated at birth was a Targhee, progeny of a ewe that did not develop clinical scrapie. The scrapie incidence in 36 at risk Suffolks removed from exposure at birth was 11%, con- siderably less -“en that expected had these animals remz d in an infected en ment.

Table 6 reflected the status of 51 goats isolated from scrapie exposure at birth, and at 6, 8 to 10, 20, 32 to 59 and 60 to 82 months of age.

None of the goats removed at birth developed scrapie, although all 5 of those alive at 5 years of age had scrapied dams and 1 also had a scrapied sire. The sire of the remaining 4 had sired 7 scrapied progeny. Under such circumstances, had they remained in an infected environment nearly all of these goats would have been expected to develop scrapie. With the exception of the 20 month group, scrapie occurred at an incidence of 25 to 100% in ali other groups and at the expected age. A further observation was that 4 of the progeny of these dairy goats, born and kept apart from any sheep, developed scrapie which suggested that goats were not "dead- end hosts" insofar as scrapie was concerned.

Table 7 recorded the fate of progeny of certain selected scrapied or free Suffolk sheep or dairy goat dams.’

Suffolk ewe G298 was scrapied at 46 months of age. She had twin lambs in 1969 and 1 lamb in 1970. All 3 lambs developed scrapie. Suffolk ewe G27a was scrapied at 39 months. Her lamb born in 1966 was scrapied at 53 months; however, her lambs born in 1967 and 1968 remained free--lived to 102 months of age.

Suffolk ewe G25a died at 131] months of age and was nega- tive clinically and histologically. Mice remained negative following intracerebral inoculation of brain, spleen, and lymph nodes from this ewe. This ewe had 9 progeny at risk, of which 4 developed scrapie and 5 did not. There was no dis- cernible pattern to the cases. In two instances, 1 twin was scrapied and 1 remained free.

Goat B259 was scrapied when 43 months old. All of her 6 progeny at risk developed scrapie.

Goat B14a remained free and died at 101 months of age. Of her 11 progeny at risk, 7 were scrapied and 4 were not.

It was observed at the Station that when scrapied dams had several progeny at risk, 1 or more progeny usually developed the disease. However, many such scrapied dams also had progeny which lived, or are living, considerably beyond the age of their dams and beyond the age animals born at the Station manifested the disease.

It was also observed that individual free dams had free progeny in earlier years followed by scrapied progeny when they were older, or had scrapied progeny when young followed by free progeny when older, or scrapie and free progeny dis- persed throughout the dam's breeding life. The same situation occurred in progeny of scrapied dams; however, the pattern was less irregular due to the smaller number of progeny from each scrapied dam and the higher incidence of scrapie in such progeny. Circumstances prevented breeding all ewes ary year and, thus, many had only 1 progeny at risk. Scrapie developed in 100% of the single progeny at risk of 11 scrapied and 15 free dams. The 26 scrapied progeny were equally divided between ewes and rams.

Table 8 reflected the difference in age scrapied of - sheep brought to the Station compared to the age scrapied of those born there. Although the average age of previously exposed sheep (Suffolks) brought to the Station did not differ greatly from the overall average, several animals brought to the Station developed the disease at quite advanced ages. The previously unexposed scrapied animals brought to the Station were also considerably older than animals born there. Progeny of scrapied dams developed the disease at a slightly younger age than did progeny of free dams. The average age was nearly the same for males and females.

DISCUSSION

snip...see full text; 


THURSDAY, AUGUST 04, 2016 

MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD 


FRIDAY, JANUARY 20, 2023 

EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES 


 FLASHBACK 2001

 Suspect symptoms

 What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 28 Mar 01 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD. 

 "This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

 2001

 Suspect symptoms 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 28 Mar 01

 Like lambs to the slaughter

 31 March 2001

 by Debora MacKenzie Magazine issue 2284.

 FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD. 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

 Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

 Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

 As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology. 

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar. 

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

 People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

 But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection." 

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

 Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.


Proc Natl Acad Sci U S A. 2001 Mar 27; 98(7): 4142–4147. Published online 2001 Mar 20. doi: 10.1073/pnas.041490898 PMCID: PMC31193 PMID: 11259641

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt– Jakob disease: Implications for human health

Corinne Ida Lasmézas,*† Jean-Guy Fournier,* Virginie Nouvel,* Hermann Boe,* Domíníque Marcé,* François Lamoury,* Nicolas Kopp,‡ Jean-Jacques Hauw,§ James Ironside,¶ Moira Bruce,‖ Dominique Dormont,* and Jean-Philippe Deslys* Author information Article notes Copyright and License information PMC Disclaimer 

ABSTRACT 

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt–Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

snip...

Characterization of the CJD and Scrapie Strains. Controls were set up by transmitting one French and one U.S. scrapie isolate from ruminants as well as French sCJD and iCJD cases from humans. None of these revealed a lesion profile or transmission characteristics similar or close to those of BSE or vCJD, respectively, thus extending to the present French scrapie isolate the previous observation that the BSE agent was different from all known natural scrapie strains (4, 24). The lesion profiles of sCJD and iCJD differed only slightly in severity of the lesions, but not in shape of the profile, revealing the identity of the causative agents. One of us reported the absence of similarity between sCJD (six cases) and U.K. scrapie (eight cases) in transmission characteristics in mice (4). Herein, we made the striking observation that the French natural scrapie strain (but not the U.S. scrapie strain) has the same lesion profile and transmission times in C57BL/6 mice as do the two human TSE strains studied. This strain “affiliation” was confirmed biochemically. There is no epidemiological evidence for a link between sheep scrapie and the occurrence of CJD in humans (25). However, such a link, if it is not a general rule, would be extremely difficult to establish because of the very low incidence of CJD as well as the existence of different isolates in humans and multiple strains in scrapie. Moreover, scrapie is transmissible to nonhuman primates (26). Thus, there is still a possibility that in some instances TSE strains infecting humans do share a common origin with scrapie, as pointed out by our findings.

''However, such a link, if it is not a general rule, would be extremely difficult to establish because of the very low incidence of CJD as well as the existence of different isolates in humans and multiple strains in scrapie. Moreover, scrapie is transmissible to nonhuman primates (26). Thus, there is still a possibility that in some instances TSE strains infecting humans do share a common origin with scrapie, as pointed out by our findings.''



Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net

Friday, April 28, 2023

Scrapie TSE Prion EU Update

Scrapie TSE Prion EU Update

Spain Scrapie Outbreak

Navarra registra el primer foco de scrapie de 2023 en España

El Ministerio de Agricultura ha notificado un foco de tembladera en una explotación de ovejas en el municipio de Ultzama

Itziar Gómez López, consejera de Desarrollo Rural y Medio Ambiente de Navarra.

Itziar Gómez López, consejera de Desarrollo Rural y Medio Ambiente de Navarra.

Francisco Ramón López - 18-04-2023 - 10:21 H - 2 min.

Este martes 18 de abril, el Ministerio de Agricultura, Pesca y Alimentación (MAPA) ha notificado un foco de scrapie, también conocida como tembladera o prurigo lumbar, en una explotación de ovejas en el municipio de Ultzama, en Navarra.

Se trata del primer foco de 2023 y según los datos del MAPA se ha producido en una explotación de 132 animales, aunque solo ha afectado a uno. En 2022 se notificaron un total de 27 focos. Entre los años 2000 y 2021 se han detectado un total de 598 focos, sin un descenso significativo.

La tembladera es un proceso neurodegenerativo progresivo que afecta a ovejas y cabras, que se clasifica como una encefalopatía espongiforme transmisible (EET) o enfermedad causada por priones.

Se divide en casos atípicos y clásicos. En lo referente a los casos atípicos de tembladera aparecen de forma natural y esporádica, mientras que la transmisión de los casos clásicos está influenciada por transmisión de la madre a su descendencia inmediatamente después del parto.

Además, se puede infectar a otros neonatos susceptibles expuestos a los fluidos expulsados durante el parto o tejidos de un animal infectado. En adultos la infección es mucho menos común y en humanos no se ha demostrado que se pueda transmitir, como sí que ocurría con la ‘enfermedad de las vacas locas’.

Según los datos del último informe de encefalopatías espongiformes transmisibles, 10 de los focos de 2021 fueron de cepas clásicas y 8 de atípicas. 


English

Navarra records the first outbreak of scrapie in 2023 in Spain

The Ministry of Agriculture has notified an outbreak of scrapie on a sheep farm in the municipality of Ultzama

Itziar Gómez López, Minister of Rural Development and Environment of Navarra.

Itziar Gómez López, Minister of Rural Development and Environment of Navarra.

Francisco Ramón López - 04-18-2023 - 10:21 a.m. - 2 min.

This Tuesday, April 18, the Ministry of Agriculture, Fisheries and Food (MAPA) has notified an outbreak of scrapie, also known as scrapie or scrapie, on a sheep farm in the municipality of Ultzama, in Navarra.

This is the first outbreak of 2023 and according to the MAPA data it has occurred on a farm with 132 animals, although it has only affected one. In 2022, a total of 27 outbreaks were reported. Between the years 2000 and 2021, a total of 598 outbreaks have been detected, without a significant decrease.

Scrapie is a progressive neurodegenerative process affecting sheep and goats, classified as a transmissible spongiform encephalopathy (TSE) or prion disease.

It is divided into atypical and classic cases. Regarding the atypical cases of scrapie, they appear naturally and sporadically, while the transmission of classic cases is influenced by transmission from the mother to her offspring immediately after delivery.

In addition, other susceptible neonates exposed to fluids expelled during delivery or tissues from an infected animal can become infected. In adults, the infection is much less common and in humans it has not been shown that it can be transmitted, as it did with 'mad cow disease'.

According to the data from the latest report on transmissible spongiform encephalopathies, 10 of the outbreaks in 2021 were from classic strains and 8 from atypical strains.


Active TSE surveillance in Great Britain and Northern Ireland



EFSA Journal 2022;20(11):7655

DOI


KEYWORDS TSE, BSE, CWD, scrapie, classical, atypical, surveillance

ON REQUEST FROM European Commission QUESTION NUMBER EFSA‐Q‐2021‐00765

CONTACT zoonoses@efsa.europa.eu

Abstract

This report presents the results of surveillance on transmissible spongiform encephalopathies (TSE) in cattle, sheep, goats, cervids and other species, and genotyping in sheep and goats, carried out in 2021 by 27 Member States (MS, EU27), the United Kingdom (in respect of Northern Ireland) (XI), and eight other non‐EU reporting countries: 

Bosnia and Herzegovina, Iceland, Montenegro, North Macedonia, Norway, Serbia, Switzerland and Turkey. 

In total, 1,021,252 cattle were tested by EU27 and XI (−9%, compared with 2020 when data from the United Kingdom were not restricted to Northern Ireland), and 66,121 cattle by eight non‐EU reporting countries, with two cases of H‐BSE in France and Spain, and four L‐BSE in France (2), Germany and Spain. 

In total, 311,174 sheep and 118,457 goats were tested in the EU27 and XI (−6.4% and −1.8%, respectively, compared to 2020 when data from the whole United Kingdom were considered). 

In sheep, 551 cases of scrapie were reported by 17 MS and XI: 

448 classical scrapie (CS) by six MS [80 index cases (IC) with genotypes of susceptible groups in 97% of the cases], 103 atypical scrapie (AS) (96 IC) by 13 MS and XI. 

In the other non‐EU reporting countries, 27,594 sheep were tested with 55 CS and 1 AS in Iceland and 8 AS in Norway. 

Ovine random genotyping was reported by nine MS and genotypes of susceptible groups accounted for 7.9%. 

In goats, 224 cases of scrapie were reported by six EU MS: 

219 CS (30 IC) by six MS, and five AS (5 IC) by three MS. 

In total, 5,854 cervids were tested for chronic wasting disease by eight MS; all resulted negative. 

Norway tested 21,670 cervids with two moose and one red deer positive. 

In total, 149 animals from four other species tested negative in Finland and Turkey.

© European Food Safety Authority


OPINION article

Front. Vet. Sci., 29 September 2020

Sec. Veterinary Infectious Diseases

Volume 7 - 2020 | https://doi.org/10.3389/fvets.2020.581969

The Epidemiology, Diagnosis and Prevention of Infectious Diseases in Livestock

Scrapie Control in EU Goat Population: Has the Last Gap Been Overcome?

Sergio Migliore*, Roberto Puleio and Guido Ruggero Loria

Istituto Zooprofilattico Sperimentale Della Sicilia “A. Mirri”, Palermo, Italy

Introduction

Scrapie is a fatal, neurodegenerative disease that affects sheep and goat worldwide, belonging to the group of transmissible spongiform encephalopathies (TSEs).

Since 2002, Member States (MS) of European Union (EU) have implemented active surveillance to control the risk of scrapie. The EU scrapie eradication policy is mainly aimed to eradicate classical scrapie. The choice of population groups and sample sizes have evolved in the years, as well as the eradication measures and control of disease (selective culling, movement restrictions, reinforced surveillance measures, etc.). In this context, over the past two decades, breeding programs to increase the frequency of the resistance-associated ARR allele in sheep populations have been introduced to minimize TSE risk in MS, but there was not a regulatory effort in adoption of analogous measures for goats. However, scientific knowledge related to scrapie resistance associated with goat PRNP gene polymorphisms has considerably expanded in the last 10 years.

Classical scrapie is considered endemic in many MS. Since its publication, the only measures applicable for TSE control in goat contained in Regulation (EC) No 999/2001 obliged farmers to provide a complete culling of whole flock, with great economic loss and serious concerns for the risk of extinction of endangered breeds. However, over the years, additional measures have been introduced such as monitoring of the infected herd without the obligation of total culling and the possibility of reintroducing goats with unknown genotype after biosafety practices. Nevertheless, these measures could allow the goat population to become the main reservoir of scrapie, affecting the disease eradication program in small ruminant population.

Following a request from the European Commission (EC), the European Food Safety Authority (EFSA) was asked to deliver scientific opinions on the scrapie situation in EU to evaluate the introduction of breeding policies in goats. From 2014, EFSA advised to promote selection and introduction of resistant bucks in EU caprine population (1). More recently, in 2017, based on the latest scientific evidence, EFSA concluded that breeding programs for scrapie resistance in goats should be implemented in MS, taking particular attention to potential negative effects of extinction in rare and endangered breeds (2).

With Regulation (EC) No 2020/772 of June 11, 2020, amending Regulation (EC) No 999/2001, EC laid down new approaches as regards eradication measures for TSEs in goats and in endangered breeds. In this context, the authors discuss advantages and critical points related to the different control measures introduced by EU regulations during the last two decades.

State of the Art

Legislative Basis

Regulation (EC) No 999/2001 establishes rules for the prevention, control, and eradication of certain TSEs, including scrapie in small ruminants. This Regulation dates back to 2001 and, after many subsequent amendments, is still in force today.

In 2003, Regulation (EC) No 260/2003 revised the requirements for eradication measures in case of the detection of TSE in a farm by selective culling of susceptible sheep and by requiring the implementation of measures to increase TSE resistance in the outbreak. Simultaneously, decision 2003/100 (EC) laid down requirements for the establishment of breeding programs for resistance to TSE in sheep, aimed to increase the level of alleles associated with resistance (ARR) and decreasing the frequency of alleles associated with susceptibility (VRQ) in EU sheep population. Commission Regulation (EC) No 1923/20065 and No 727/2007 then integrated the breeding program requirements into Regulation (EC) No 999/2001. In 2006, EFSA confirmed the efficacy of breeding program for TSE resistance in sheep (3).

More recently, on June 11, 2020, Regulation (EC) No 2020/772 amended Annexes I, VII, and VIII to Regulation (EC) No 999/2001 introducing the possibility for the MS to limit slaughtering/culling and destruction to goats which are genetically susceptible to classical scrapie. In addition, the definition of “endangered breed” of Regulation (EU) 2016/1012 replaced the expression of “local breed in danger of being lost to farming” as laid down in Regulation (EU) No 807/2014 (4).

Scrapie in EU Goats

Classical scrapie shows similar epidemiological features in sheep and goats and the involvement of both species in outbreaks is common. Even if the incidence in goats is much lower than in sheep, milk and placenta of infected goats may serve as sources of infection to sheep (5, 6). Scrapie in goat was described for the first time in 1942 (4); since then, clinical cases have been recorded throughout Europe. Animal movements between herds and environmental contamination play relevant roles as risk factors.

In 2019, a total of 325,386 sheep and 138,128 goats were tested in EU. In sheep, 821 cases of classical scrapie were detected in seven MS, whereas 517 cases were reported in goats in seven MS (7). Scrapie in goat is considered endemic in the EU countries with the largest caprine populations with more than 10,500 cases from 2002 to 2017. Between 2002 and 2015, classical scrapie was detected in 10 MS with 2.4 cases out of 10,000 tested heads. In this prevalence study, Cyprus was excluded due to an epidemic over the last 10 years (2).

Genetic Basis

In the last two decades, an extensive review of literature was conducted to identify relevant alleles of goat PRNP to which a breeding program could be based. These studies were conducted within different MS and goat breeds. A considerable dataset has been produced for the following alleles: S127, M142, R143, D145, D146, S146, H154, Q211, and K222. Among them, K222, D146, and S146 alleles confer higher genetic resistance to classical scrapie strains circulating in the EU goat population (2). In 2017, based on a combination of the “weight of evidence” and the “strength of resistance,” EFSA provided a ranking of resistance to classical scrapie, as follows: K222 > D146 = S146 > Q211 = H154 = M142 > S127 = H143 > wild type (2).

Goat Breeding in EU

Goat farming plays an important socioeconomic role in several countries, particularly where there are hills and mountains, and remote, marginal, and even semi-arid areas (8, 9). Europe is the continent with the widest caprine biodiversity with 187 goat breeds, which is 33% of the goat breeds acknowledged worldwide (10). In this context, there are breeds with large population sizes, cosmopolitan and often characterized by a high production, and breeds with small population sizes not yet subjected to conservation programs because of their remoteness or because they are less competitive in terms of production than other selected breeds (9). Such different scenarios obviously have required a different scrapie control strategy.

Discussion

In 2017, EFSA, based on prolonged field experience and experimental studies, concluded that the K222, D146, and S146 variants confer genetic resistance to the classical scrapie strain circulating in the EU goat population (2). EFSA highlighted that the protective effect of K222 is greater than D146 and S146 variants and of ARR allele in sheep, when the 2002 Scientific Steering Committee opinion was published (2). In this regard, a substantial difference between sheep and goats in the new Regulation (EC) No 2020/772 still remains. In sheep, the ARR/ARR homozygous genotype in reproductive males is an essential requirement, whereas in goats, heterozygosity for at least one of K222 and D/S146 alleles is sufficient to avoid the stamping out. It should be remembered that heterozygous variants Q222K and N146S/D in goats do not confer full protection against classical scrapie as reported in natural outbreaks in Greece (11) and in Cyprus (12). In addition, the subsequent restocking of outbreak without genotype consideration after biosafety practices is a considerable risk. These are critical points whose efficacy will be assessed in the future.

The EFSA opinion also highlights that a high selective pressure in some breeds with a low frequency of resistant variants would likely have an adverse effect on genetic diversity and that each MS should be able to design its own genetic selection strategy depending on the breed concerned.

Estimating the frequency of candidate alleles is a preliminary step in understanding the feasibility of a breeding program. Several investigations on goat PRNP were performed in MS in recent years, and some breed-related differences emerged (Table 1). Higher frequency (>24.5%) of 146D or S variants was described in cosmopolitan Boer goat in Great Britain and Netherlands (13–15) and in native Damascus and related breeds in Cyprus (16.5%) (17). A lower frequency (3%) was also described in local and crossbred in Greece (16). To date, this mutation does not seem to be widespread in other MS. In contrast, 222 K variant seems to be more common across the MS. Frequencies between 1.2 and 7.5% were described in cosmopolitan and large population size breeds such as Saanen (1.2–4%) and Alpine (6.4–7.5%) reared in Spain, Netherlands, Italy, France, and Greece (15, 16, 18–20). Very high frequency (29.5%) was described in Dutch Toggenburg in Netherlands (15). Variable frequencies were described in small size of native breeds such as local and crossbred in Greece (0.3–5.6%) (16). In Italy, where a great caprine biodiversity is present, a difference between northern and southern native breeds was described (20), with higher frequencies of 222 K in Southern breed such as Garganica (17.2%), Ionica (7.2%), southern crossbred (22.5%), Girgentana (18.7%), Rossa Mediterranea (12.7%), Argentata dell'Etna (16.3%), Aspromontana (10.3%), and Cilentana (18.2%) (20–23). Many of these breeds are considered in critical or endangered status (24) and for this reason any breeding program should consider the endangered status of each goat population to preserve the genetic variability and the biodiversity together with disease control (21).

Table 1 www.frontiersin.org TABLE 1. Breeds with S146/D146 and K222 haplotypes reported in literature and their frequencies reported in EU.

Various mutations in the PRNP in different breeds have potentially been positively selected in relation to local circulating scrapie strains originating in specific environmental conditions (25).

A recent study (26) assessed the impact of different breeding strategies in goat using a mathematical model, and it concluded that breeding programs for scrapie resistance could be implemented also in a context of so high biodiversity and also different size of the populations of goats. Nevertheless, the growth rate of resistant goats in some breeds may be slow due to the initial genetic profile not being particularly favorable inside the breed. In cosmopolitan breeds with a large population size, a breeding program in the overall population would be desirable. In contrast, in endangered breeds with a small population, a breeding program should be implemented starting from reproductive nuclei. This scheme is less expansive and protects the endangered breeds even if it takes longer to reach the expected results.

As well as goat breeds, a breeding program for scrapie resistance should consider the particular situation of each MS in terms of the presence of resistant alleles and their relative frequency. For example, in Greece, which has one of the largest goat populations in Europe, a goat-scrapie resistance program targeting the Q211, S146, and K222 alleles was designed (27), whereas in Italy, pilot projects selected positively a singular variant K222.

Although there is a strong interest in disease control among goat farmers in the Northern MS, breeding for resistance is often compromised by the low frequency of resistant alleles. By contrast, in Southern MS where a satisfying frequency of resistant alleles is present, goat farming is mainly related to pastoralism and in several cases there is a lack of interest in starting genetic programs. For this reason, to be successful, new regulations have to consider engaging farmers' cooperation by appropriate risk communication and involving them in the genetic program as well as providing an adequate financial support for goat genotyping.

Regulation (EC) No 2020/772 laid down an alternative tool for scrapie control in EU goat population. It particularly recognized the genetic resistance to classical scrapie in goats carrying at least one of the most recognized alleles (K222, D146, and S146) and preserving them from culling in the case of outbreak. In addition, the new regulation introduces possible derogation measures for endangered breeds according to Regulation (EU) 2016/1012. This new measure will finally strengthen the control of TSEs in small ruminants in the EU and will also have beneficial effects on farming system and for the conservation of goat breed biodiversity.


''In 2019, a total of 325,386 sheep and 138,128 goats were tested in EU. In sheep, 821 cases of classical scrapie were detected in seven MS, whereas 517 cases were reported in goats in seven MS (7). Scrapie in goat is considered endemic in the EU countries with the largest caprine populations with more than 10,500 cases from 2002 to 2017. Between 2002 and 2015, classical scrapie was detected in 10 MS with 2.4 cases out of 10,000 tested heads. In this prevalence study, Cyprus was excluded due to an epidemic over the last 10 years (2).'' 


atypical Scrapie

***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.

SNIP...SEE;

THURSDAY, JULY 8, 2021 

EFSA Scientific report on the analysis of the 2‐year compulsory intensified monitoring of atypical scrapie

***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.





Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies

Location: Virus and Prion Research

Title: Transmission of the atypical/nor98 scrapie agent to suffolk sheep with VRQ/ARQ, ARQ/ARQ, and ARQ/ARR genotypes

Author

item Cassmann, Eric

item MAMMADOVA, JAJIBA - Orise Fellow

item BENESTAD, SYLVIE - Norwegian Veterinary Institute

item MOORE, SARA JO - Orise Fellow

item Greenlee, Justin

Submitted to: PLoS ONE

Publication Type: Peer Reviewed Journal

Publication Acceptance Date: 1/21/2021

Publication Date: 2/11/2021

Citation: Cassmann, E.D., Mammadova, J., Benestad, S., Moore, S., Greenlee, J.J. 2021. Transmission of the atypical/nor98 scrapie agent to suffolk sheep with VRQ/ARQ, ARQ/ARQ, and ARQ/ARR genotypes. PLoS ONE. 16(2). Article e0246503. https://doi.org/10.1371/journal.pone.0246503.


Interpretive Summary: Atypical scrapie is a prion disease that affects sheep. Unlike classical scrapie, atypical scrapie is thought to occur spontaneously, and it is unlikely to transmit between sheep under natural conditions. Another notable distinction between classical and atypical scrapie is the prion protein genotype of afflicted sheep and the locations in the brain where misfolded prions accumulate. Atypical scrapie generally occurs in sheep that are resistant to classical scrapie. Misfolded prions are predominantly found in the cerebellum for atypical scrapie and not in the brainstem as seen with classical scrapie. Atypical scrapie is a relevant disease because of its potential association with other prion diseases. Some research has shown that the atypical scrapie agent can undergo a transformation of disease forms that makes it appear like classical scrapie or classical bovine spongiform encephalopathy (mad cow disease). Therefore, atypical scrapie is thought to be a possible source for these prion diseases. We investigated the transmission of the atypical scrapie agent to sheep with three different prion protein genotypes. A diagnosis of atypical scrapie was made in all three genotypes of sheep. Misfolded prion protein was detected earliest in the cerebellum and the retina. This is the first report describing the early accumulation of misfolded prions in the retina of sheep with atypical scrapie. Understanding where misfolded prions accumulate in cases of atypical scrapie can lead to better detection earlier in the disease. Furthermore, the materials derived from this experiment will aid in investigating origins of other prion diseases.

Technical Abstract: Scrapie is a transmissible spongiform encephalopathy that occurs in sheep. Atypical/Nor98 scrapie occurs in sheep with that tend to be resistant to classical scrapie and it is thought to occur spontaneously. The purpose of this study was to test the transmission of the Atypical/Nor98 scrapie agent in three genotypes of Suffolk sheep and characterize the distribution of misfolded prion protein (PrPSc). Ten sheep were intracranially inoculated with brain homogenate from a sheep with Atypical/Nor98 scrapie. All sheep with the ARQ/ARQ and ARQ/ARR genotypes developed Atypical/Nor98 scrapie confirmed by immunohistochemistry, and one (1/3) sheep with the VRQ/ARQ genotype had detectable PrPSc consistent with Atypical/Nor98 scrapie at the experimental endpoint of 8 years. Sheep with mild early accumulations of PrPSc in the cerebellum had concomitant retinal PrPSc. Accordingly, large amounts of retinal PrPSc were identified in clinically affected sheep and sheep with dense accumulations of PrPSc in the cerebellum.


***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.


O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 

PRION 2015 CONFERENCE


***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 


TUESDAY, APRIL 4, 2023 

Iceland Reports Another Case of Scrapie 


MONDAY, SEPTEMBER 13, 2021 

New case of scrapie in Iceland Skagafjörður 


FRIDAY, JANUARY 08, 2021 

Canada Scrapie Flock Certification Program 


TUESDAY, FEBRUARY 08, 2022 

Romania Outbreaks of scrapie in two sheep farms 750 animals are affected


FRIDAY, JANUARY 20, 2023 

EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES 


WEDNESDAY, FEBRUARY 03, 2021 

Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al


WEDNESDAY, MARCH 16, 2022 

SHEEP BY-PRODUCTS AND WHAT ABOUT Scrapie TSE PrP and Potential Zoonosis? 


WEDNESDAY, DECEMBER 8, 2021 

Importation of Sheep, Goats, and Certain Other Ruminants AGENCY: Animal APHIA, USDA, FINAL RULE [Docket No. APHIS–2009–0095] RIN 0579–AD10


FRIDAY, DECEMBER 10, 2021 

USDA APHIS National Scrapie Eradication Program October 2021 Monthly Report Fiscal Year 2022


MONDAY, NOVEMBER 29, 2021 

Experimental Oronasal Transmission of Chronic Wasting Disease Agent from White-Tailed Deer to Suffolk Sheep Volume 27, Number 12—December 2021 Dispatch


FRIDAY, DECEMBER 10, 2021 

Scrapie at Abattoir: Monitoring, Control, and Differential Diagnosis of Wasting Conditions during Meat Inspection 


Terry S. Singeltary Sr.